POS0257 COMPARISON OF SARS-CoV-2 VACCINE RESPONSE IN PATIENTS WITH INFLAMMATORY RHEUMATIC DISEASE; mRNA-1273 VACCINE INDUCES HIGHER HUMORAL IMMUNOGENICITY THAN BNT162b2
Authors: Y. Kondo, M. Takeshita, Y. Uwamino, H. Namkoong, S. Saito, J. Kikuchi, H. Hanaoka, K. Suzuki, N. Hasegawa, M. Murata, Y. Kaneko
Journal: Annals of the Rheumatic Diseases (2022)

Background The SARS-CoV-2 messenger RNA (mRNA) vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) have benefitted all countries amid the coronavirus disease 2019 (COVID-19) crisis. Whereas both of them have shown efficacy in preventing COVID-19 illness in healthy participants, there is paucity of data about immunogenicity and safety of mRNA COVID-19 vaccines in patients with autoimmune, inflammatory rheumatic disease. Recent observational studies evaluated mainly BNT162b2, suggesting that glucocorticoids, immunosuppressive agents impair SARS-CoV-2 vaccine responses. However, difference in immune reactions and safety between BNT162b2 and mRNA-1273 have not been clarified in patients with inflammatory rheumatic diseases. Objectives To assess humoral and T cell immune responses and safety profiles after two doses of different mRNA vaccine against SARS-CoV-2; BNT162b2 and mRNA-1273. Methods We enrolled consecutive, previously uninfected patients with inflammatory rheumatic diseases receiving mRNA vaccine including BNT162b2 and mRNA-1273. Healthy participants receiving BNT162b2 were also recruited as control. Blood samples were obtained 3weeks, 2 months, 3 months, 4 months, and 6 months after second dose of vaccines. We measured titres of neutralizing antibodies against SARS-CoV-2 and calculated seroconversion rates to evaluate humoral responses. We also assessed T-cell immunity responses by using interferon releasing assay against SARS-CoV-2 in a part of the patients. Answers to questionnaires about adverse reactions were obtained from participants. Results A total of 974 patients with inflammatory rheumatic diseases and healthy 630 control participants were enrolled. Among them, 796 patients received BNT162b2, 178 patients received mRNA-1273, and all control participants received BNT162b2. Seroconversion rates and neutralizing antibody titres 3 weeks after vaccination were significantly higher in patients with mRNA-1273 and healthy participants with BNT162b2 compared with patients with BNT162b2; seroconversion rates, 97.2% vs 99.5% vs 83.3%, p&lt;0.001; titers of neutralizing antibodies, 29.4±33.9 IU/mL vs 23.9±14.2 IU/mL vs 10.8±16.5 IU/mL, p&lt;0.001, respectively. On another front, T cell reaction against SARS-CoV-2 was similar in both patients with mRNA-1273 and BNT162b2; interferon gamma levels for antigen 1, 1.2±2.1 IU/mL vs 0.8±2.5 IU/mL, p=0.23; and for antigen 2, 1.4±1.9 IU/mL vs 1.0±2.1 IU/mL, p=0.11, respectively. Regarding adverse reaction of each mRNA vaccine, the frequency of systemic adverse reactions including fever and general fatigue are also significantly higher in patients with mRNA-1273 and healthy controls than patients with BNT162b2; fever, 48.0% vs 44.9% vs 10.2%, p&lt;0.001; general fatigue, 70.4% vs 61.8% vs 31.2%, p&lt;0.001, respectively). In longitudinal measurement, neutralizing antibody titres in patients with BNT162b2 were decreased more rapidly than those in healthy controls; 3.3±3.2 IU/mL in patients with BNT162b2 at 4 months and 3.2±4.7 IU/mL in healthy controls with BNT162b2 at 6 months. We identified age, glucocorticoid dose (prednisolone &gt; 7.5mg), use of immunosuppressants including methotrexate, mycophenolate, cyclophosphamide, and tacrolimus are associated with rapid attenuation of humoral responses in patients with BNT162b2. Conclusion Our results demonstrated a significant higher humoral immunogenicity and frequency of systemic adverse reaction of the SARS-CoV-2 mRNA-1273 (Moderna) compared with the BNT162b2 (Pfizer-BioNTech) in inflammatory rheumatic disease patients. Glucocorticoid and immunosuppressive agents impaired induction and sustention of neutralizing antibody, and earlier third booster vaccination may be required within 4 months, especially for those receiving BNT162b2. References [1]Steensels D, Pierlet N, Penders J et al. JAMA. 2021;326(15):1533–1535. [2]Friedman MA, Curtis JR and Winthrop KL. Ann Rheum Dis 2021;80:1255–1265. Disclosure of Interests None declared